- Email: [email protected]
ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CARCINOMA IN PATIENTS WITH HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME)
THE JOURNAL OF UROLOGY®
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
374 EXPERIENCE WITH COMPLEX PERCUTANEOUS RESECTIONS FOR UPPER TRACT UROTHELIAL CARCINOMA Brian H Irwin*, Andre Berger, Ricardo Brandina, Cleveland, OH; David Canes, Burlington, MA; Armine K Smith, Sebastien Crouzet, Georges-Pascal Haber, Kazumi Kamoi, Robert J Stein, Mihir M Desai, Cleveland, OH INTRODUCTION AND OBJECTIVE: Percutaneous endoscopic resection is a viable treatment option for upper tract urothelial carcinomas (UC) in carefully selected patients. We present our experience with patients who have undergone percutaneous endoscopic therapy for complex tumors. METHODS: Patients undergoing endoscopic treatment for UC were identified within a prospectively maintained patient database at a single institution. Charts were reviewed to identify complex patients who met at least one of the following criteria: (a) tumor size >2.5cm, (b) preoperative creatinine level >3.0, or (c) anatomical variant such as autotransplanted kidneys, prior partial nephrectomy of effected kidney or prior cystectomy/urinary diversion. Demographic, operative, and oncologic data were captured. Recurrence free, disease specific and overall survivals were calculated for both the complex and the non-complex cases. RESULTS: A total of 48 patients were identified who underwent endoscopic treatment for upper tract UC since 1985. Of these, 17 patients met the criteria for complex resections (tumors >2.5cm (N=9), pre-op creatinine>3.0 (N=3), prior partial nephrectomy (N=2), prior cystectomy (N=2), prior distal ureterectomy (N=1), auto-transplanted kidney (N=1)) with a median follow-up of 22 months. No difference was found between the two groups with regard to mean age (70.3±10.3 years in noncomplex cases versus 69.5±10.9 years in complex cases), complication rate (4% versus 6%) or change in creatinine (1.30 to 1.25 versus 1.40 to 1.38). The incidences of high grade tumors (40% in non-complex cases versus 60% in complex cases), invasive tumors (18% versus 18%), prior contralateral nephroureterectomy (46% versus 56%) and history of prior bladder cancers (52% versus 42%) were similar between the two groups. Patients in the non-complex group were less likely to have solitary kidneys (32% versus 92%) and larger tumors (1.48 ± 0.65cm versus 3.13 ± 0.79cm). No difference was seen cancer specific survival (P=0.97). Improved trends in overall survival (P=0.14) and recurrence free survival (P=0.08) were seen in the non-complex groups when compared to the complex group. CONCLUSIONS: These findings suggest that patients with large tumors, poor renal function and significant anatomical variations may be well served by endoscopic treatment for upper tract UC. These resections may be both safe and feasible even in patients who might be thought to be at high risk for technical and physiologic complications. Source of Funding: None
375 LONG TERM ONCOLOGICAL OUTCOMES FOR UPPER TRACT UROTHELIAL CARCINOMA: ENDOSCOPIC TREATMENT VERSUS NEPHROURETERECTOMY Andre Berger*, Ricardo Brandina, Brian H Irwin, Kazumi Kamoi, Sebastien Crouzet, Georges-Pascal Haber, David Canes, Robert J Stein, Monish Aron, Inderbir S Gill, Mihir M Desai, Cleveland, OH INTRODUCTION AND OBJECTIVE: To compare longterm oncological outcomes following endoscopic treatment and nephroureterectomy (NU) either open or laparoscopic for upper tract transitional cell carcinoma (TCC). METHODS: Between April 1992 and January 2008, 45 patients (76% with solitary kidneys) underwent endoscopic treatment (percutaneous or ureteroscopic) with curative intent and 402 underwent NU (216 laparoscopic and 186 open) for upper tract TCC at our institution. Data were obtained from a prospectively maintained database, patient charts, telephone follow-up and a review of the Social Security Death Index. RESULTS: There were no significant differences between the endoscopic and NU groups as regards mean patient age (70vs. 70 yrs),
135
ASA class and comorbidities. Mean follow-up was 44 and 43 months, respectively. Most patients presented with high grade disease (56% vs. 74% p= 0.01). Five-year overall, cancer-specific survival and recurrencefree survival in the endoscopic group and NU group were, respectively, 56%, 78% and 55% vs. 56%, 78% and 59% (p > 0.05 for all). Tumor grade was the only independent prognostic factor for both cancer-specific (p= 0.02) and recurrence-free survival on a multivariate analysis (p = 0.03). Even after analyzing survival by grade, no statically significant difference was found between the groups. CONCLUSIONS: Long-term oncological outcomes after endoscopic treatment for upper tract TCC comparable to extirpative procedure either in low grade or high grade disease. It can be recommended as an alternative to nephroureterectomy in selected patients. Source of Funding: None
376 ORGAN-SPARING TREATMENT OF NON MUSCLE-INVASIVE UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA: A MULTI-INSTITUTIONAL EXPERIENCE Ardeshir R Rastinehad*, Long Island, NY; Gianluca Giannarini, George N Thalmann, Urs E Studer, Bern, Switzerland; Arthur D Smith, Long Island, NY INTRODUCTION AND OBJECTIVE: To determine whether the use of Bacillus Calmette-Guèrin (BCG) in the organ-sparing treatment of non muscle-invasive (NMI) upper urinary tract (UUT) transitional cell carcinoma (TCC) has an oncological benefit. METHODS: We retrospectively analyzed the combined series of 118 renal units (RU) in 111 patients (mean age 69.7±11.5 years) treated for NMI UUT TCC. Three approaches were utilized: primary BCG perfusion for RU with carcinoma in situ (CIS) (n=31), and percutaneous resection with (n=54) or without (n=33) adjuvant BCG perfusion for RU with papillary NMI tumors. Recurrence was defined as positive selective UUT cytology after obtaining negative cytology for RU with CIS, and positive biopsy after the 3-month nephroscopy for RU undergoing resection. Progression was defined as an increase in grade or stage of primary tumor at time of recurrence. For the purpose of analysis, RU were stratified by initial treatment modality, primary BCG perfusion versus percutaneous resection. RU undergoing percutaneous resection were stratified by adjuvant BCG therapy. Outcome measures were recurrence, progression, and renal preservation rate, time to recurrence and overall survival. Chi-square and independent t tests were used for comparison of all outcome measures between these strata. RESULTS: Mean and median follow up was 61.8±55.8 and 42 months, respectively. There was no statistical difference in tumor grade or stage between BCG-treated and non-treated RU (p>.05). Overall progression rate was 19.9%, diminishing to 6.5% for RU with CIS. Overall renal preservation rate was 84.7%, reaching 93.5% for RU with CIS. No statistically significant difference between the above mentioned strata was found in the outcome measures (p>.05). All results are detailed in the table. CONCLUSIONS: Our data suggests that organ-sparing treatment of NMI UUT TCC yields a relatively high (>75%) renal preservation rate. The use of adjuvant BCG therapy after resection appeared not to have an impact on recurrence, progression, renal preservation rate, time to recurrence, and overall survival. BCG perfusion seems to give the best results in patients with UUT CIS. Source of Funding: None
377 ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CARCINOMA IN PATIENTS WITH HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME) Scott G Hubosky*, Sarah Charles, Bruce Bowman, Demetrius H Bagley, Philadelphia, PA INTRODUCTION AND OBJECTIVE: Hereditary nonpolyposis colorectal cancer is a genetic disorder associated with extracolonic
136
THE JOURNAL OF UROLOGY®
malignancies including upper tract urothelial carcinoma of the ureter and renal pelvis. The disorder is characterized by mutations in DNA mismatch repair genes including MSH-2 and MLH-1. Patients tend to present at younger ages compared to sporadic cases of upper tract urothelial cancer and the incidence of bilateral renal involvement is unknown in this particular population. We retrospectively studied the clinical characteristics and outcomes of 10 patients with HNPCC to determine the efficacy of endourological management and surveillance. METHODS: Our experience with ureteroscopic management of upper tract urothelial carcinoma was retrospectively reviewed and 8 patients were identified having MSH-2 genetic mutations consistent with HNPCC; 2 patients are pending genetic workup but provide strong clinical suspicion for HNPCC based on personal and family history. Records were reviewed to determine age at presentation, bilaterality of disease, number of surveillances, months of follow-up and disease progression. RESULTS: No patients developed metastatic upper tract urothelial carcinoma; one died of metastatic colon cancer after a third recurrence. Mean age at presentation was 57 years (40 - 73), mean number of surveillances was 10.2 (2 - 30), mean months of followup 48 (3 - 152). 40% of patients had bilateral disease; 6 patients had ureteral involvement and 4 patients had renal pelvis involvement. All cases presented as grade 1-2 and no cases progressed to grade 3. One nephroureterectomy was performed after ureteral stricture development; final pathology showed CIS of the renal pelvis. CONCLUSIONS: This series is the first reported on HNPCC patients with upper tract urothelial involvement undergoing endoscopic surveillance and treatment. Endoscopic management is attractive in this patient population in which relatively younger patients may present with bilateral disease. Close endoscopic surveillance is paramount to avoid disease progression. Source of Funding: None
378 ODMIT C: A PROSPECTIVE RANDOMISED MULTICENTRE TRIAL OF A SINGLE POST-OPERATIVE DOSE OF INTRAVESICAL MITOMYCIN C TO PREVENT BLADDER CANCER FORMATION FOLLOWING NEPHROURETERECTOMY FOR UPPER TRACT TCC ( UTTCC) Tim S O’Brien*, Raj Singh, Eleanor Ray, Bola Coker, Ralph Beard, London, United Kingdom; BAUS Section of Oncology INTRODUCTION AND OBJECTIVE: Bladder tumours are reported in upto 40% of patients following surgery for an upper tract TCC. The evidence suggests that many of these bladder tumours may be implantation metastases. Reducing this risk of bladder tumour formation would be a valuable contribution in the management of these patients. Prophylactic intravesical chemotherapy has never been formally tested in this regard. METHODS: Patients with UTTCC and no previous history of bladder cancer were entered by 46 centres in the UK between July 2000 and December 2006. Patients were randomised to receive standard care or a single post operative dose of 40 mg intravesical Mitomycin-C on removal of the urethral catheter following nephroureterectomy. Follow up was by cystoscopy at 3/12, 6/12 and 12/12. The primary endpoint was the development of bladder tumour within the first year post-nephroureterectomy. The trial was supported by BAUS sub-section of Oncology. RESULTS: 284 patients were randomised. The number of cases per centre ranged from 1-21. The arms were well matched for age and tumour multifocality; however in the mitomycin treated arm there were more grade 3 tumours (51 versus 43). There were 31 exclusions ( 6 no tumour; 8 RCC; 3 other tumour not TCC; 11 protocol violations; 3 others ). There were no reported serious adverse effects from Mitomycin C. 5 patients were unable to retain the mitomycin for one hour. By intention to treat, bladder recurrence occurred in 21/122 (17%) of the mitomycin arm and 33/123 (26%) of the observation arm (P = 0.05). By treatment received, bladder recurrence occurred in 17/106 (16%) of the mitomycin arm and 31/119 (26%) of the observation arm (P = 0.03). Bladder tumour was identified in 1/18 (6%) patients who had Grade 1 UTTCC; 31/122 (25%) who had grade 2 UTTCC;
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
and 20/94 (21%) who had Grade 3 UTTCC. The number needed to treat to prevent one bladder tumour in the first year post surgery is 10. CONCLUSIONS: A single intravesical dose of mitomycin-C helps prevent bladder tumour formation following nephroureterectomy for TCC. It should be considered in all patients. Source of Funding: £4000 was received from Kyowa to defer administrative costs of the trial
379 DO CHANGES IN RENAL FUNCTION FOLLOWING NEPHROURETERECTOMY IMPACT THE USE OF PERIOPERATIVE CHEMOTHERAPY? Rebecca L. O’Malley*, Matthew Kaag, Padraic O’Malley, Guilherme Godoy, New York, NY; Mang L Chen, Marc C. Smaldone, Ronald L. Hrebinko, Jr, Pittsburgh, PA; Kinjal C Vora, Bernard H Bochner, Guido Dalbagni, Michael D Stifelman, Samir S. Taneja, William C. Huang, New York, NY INTRODUCTION AND OBJECTIVE: Upcoming 2009 NCCN (National Comprehensive Cancer Network) guidelines for the management of upper tract transitional cell carcinoma (UTTCC) suggest that cisplatin-based chemotherapy (CBCT) in combination with surgery should be considered in selected patients. Unfortunately there is no level I evidence demonstrating the appropriate timing or efficacy of perioperative chemotherapy in UTTCC. Delivery of CBCT requires adequate renal function which may be significantly impaired following nephroureterectomy (NU). As a result we speculate that a significant number of patients may become ineligible for CBCT following NU. METHODS: We combined 3 institutional databases and identified 324 patients having undergone NU from 1991 to 2008. Patients receiving preoperative chemotherapy were excluded. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) by the Modification by Diet in Renal Disease equation (eGFR = 186 x [Serum Cr] -1.154 x Age-0.203 x [1.21 if African-American] x [0.742 if Female]). The serum Cr level drawn prior to surgery and the level drawn nearest to 3 months postoperatively (range 2 weeks-12 months) but prior to initiation of postoperative chemotherapy were utilized. Based on current cisplatinbased regimens for transitional cell carcinoma of the bladder we used estimated eGFRs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2 as potential eligibility cutoffs for CBCT. RESULTS: The median age of our cohort was 71 (IQR 63, 77), 9 (3%) were African-American and 192 (59%) were male. Based on cutoffs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2, 44% and 78% of patients respectively were eligible for CBCT prior to NU. Following NU only 15% and 53% remained eligible for CBCT based on cutoffs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2, respectively. The reduction in eligible patients demonstrated statistical significance by either cutoff (p<0.001 for both). Of the 112 patients with borderline GFR (45 - 60 ml/ min/1.73m2) prior to NU, only 50 (45%) remained eligible for modified CBCT regimens following NU. CONCLUSIONS: For UTTCC there is a significant need for appropriately designed clinical trials assessing the timing and use of perioperative chemotherapy. Given the current findings the design of these trials must take into account the impact of NU on the eligibility of these patients for CBCT. Source of Funding: None
380 DEVELOPMENT OF CHRONIC KIDNEY DISEASE AFTER NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA AND IMPLICATIONS FOR THE ADMINISTRATION OF CISPLATIN-BASED CHEMOTHERAPY Brian R Lane*, Armine K Smith, Benjamin T Larson, Michael C Gong, Inderbir S Gill, Steven C Campbell, Andrew J Stephenson, Cleveland, OH INTRODUCTION AND OBJECTIVE: Neoadjuvant cisplatinbased chemotherapy (GC/MVAC) improves the survival of patients with invasive bladder cancer and adjuvant GC/MVAC is justified largely by
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
374 EXPERIENCE WITH COMPLEX PERCUTANEOUS RESECTIONS FOR UPPER TRACT UROTHELIAL CARCINOMA Brian H Irwin*, Andre Berger, Ricardo Brandina, Cleveland, OH; David Canes, Burlington, MA; Armine K Smith, Sebastien Crouzet, Georges-Pascal Haber, Kazumi Kamoi, Robert J Stein, Mihir M Desai, Cleveland, OH INTRODUCTION AND OBJECTIVE: Percutaneous endoscopic resection is a viable treatment option for upper tract urothelial carcinomas (UC) in carefully selected patients. We present our experience with patients who have undergone percutaneous endoscopic therapy for complex tumors. METHODS: Patients undergoing endoscopic treatment for UC were identified within a prospectively maintained patient database at a single institution. Charts were reviewed to identify complex patients who met at least one of the following criteria: (a) tumor size >2.5cm, (b) preoperative creatinine level >3.0, or (c) anatomical variant such as autotransplanted kidneys, prior partial nephrectomy of effected kidney or prior cystectomy/urinary diversion. Demographic, operative, and oncologic data were captured. Recurrence free, disease specific and overall survivals were calculated for both the complex and the non-complex cases. RESULTS: A total of 48 patients were identified who underwent endoscopic treatment for upper tract UC since 1985. Of these, 17 patients met the criteria for complex resections (tumors >2.5cm (N=9), pre-op creatinine>3.0 (N=3), prior partial nephrectomy (N=2), prior cystectomy (N=2), prior distal ureterectomy (N=1), auto-transplanted kidney (N=1)) with a median follow-up of 22 months. No difference was found between the two groups with regard to mean age (70.3±10.3 years in noncomplex cases versus 69.5±10.9 years in complex cases), complication rate (4% versus 6%) or change in creatinine (1.30 to 1.25 versus 1.40 to 1.38). The incidences of high grade tumors (40% in non-complex cases versus 60% in complex cases), invasive tumors (18% versus 18%), prior contralateral nephroureterectomy (46% versus 56%) and history of prior bladder cancers (52% versus 42%) were similar between the two groups. Patients in the non-complex group were less likely to have solitary kidneys (32% versus 92%) and larger tumors (1.48 ± 0.65cm versus 3.13 ± 0.79cm). No difference was seen cancer specific survival (P=0.97). Improved trends in overall survival (P=0.14) and recurrence free survival (P=0.08) were seen in the non-complex groups when compared to the complex group. CONCLUSIONS: These findings suggest that patients with large tumors, poor renal function and significant anatomical variations may be well served by endoscopic treatment for upper tract UC. These resections may be both safe and feasible even in patients who might be thought to be at high risk for technical and physiologic complications. Source of Funding: None
375 LONG TERM ONCOLOGICAL OUTCOMES FOR UPPER TRACT UROTHELIAL CARCINOMA: ENDOSCOPIC TREATMENT VERSUS NEPHROURETERECTOMY Andre Berger*, Ricardo Brandina, Brian H Irwin, Kazumi Kamoi, Sebastien Crouzet, Georges-Pascal Haber, David Canes, Robert J Stein, Monish Aron, Inderbir S Gill, Mihir M Desai, Cleveland, OH INTRODUCTION AND OBJECTIVE: To compare longterm oncological outcomes following endoscopic treatment and nephroureterectomy (NU) either open or laparoscopic for upper tract transitional cell carcinoma (TCC). METHODS: Between April 1992 and January 2008, 45 patients (76% with solitary kidneys) underwent endoscopic treatment (percutaneous or ureteroscopic) with curative intent and 402 underwent NU (216 laparoscopic and 186 open) for upper tract TCC at our institution. Data were obtained from a prospectively maintained database, patient charts, telephone follow-up and a review of the Social Security Death Index. RESULTS: There were no significant differences between the endoscopic and NU groups as regards mean patient age (70vs. 70 yrs),
135
ASA class and comorbidities. Mean follow-up was 44 and 43 months, respectively. Most patients presented with high grade disease (56% vs. 74% p= 0.01). Five-year overall, cancer-specific survival and recurrencefree survival in the endoscopic group and NU group were, respectively, 56%, 78% and 55% vs. 56%, 78% and 59% (p > 0.05 for all). Tumor grade was the only independent prognostic factor for both cancer-specific (p= 0.02) and recurrence-free survival on a multivariate analysis (p = 0.03). Even after analyzing survival by grade, no statically significant difference was found between the groups. CONCLUSIONS: Long-term oncological outcomes after endoscopic treatment for upper tract TCC comparable to extirpative procedure either in low grade or high grade disease. It can be recommended as an alternative to nephroureterectomy in selected patients. Source of Funding: None
376 ORGAN-SPARING TREATMENT OF NON MUSCLE-INVASIVE UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA: A MULTI-INSTITUTIONAL EXPERIENCE Ardeshir R Rastinehad*, Long Island, NY; Gianluca Giannarini, George N Thalmann, Urs E Studer, Bern, Switzerland; Arthur D Smith, Long Island, NY INTRODUCTION AND OBJECTIVE: To determine whether the use of Bacillus Calmette-Guèrin (BCG) in the organ-sparing treatment of non muscle-invasive (NMI) upper urinary tract (UUT) transitional cell carcinoma (TCC) has an oncological benefit. METHODS: We retrospectively analyzed the combined series of 118 renal units (RU) in 111 patients (mean age 69.7±11.5 years) treated for NMI UUT TCC. Three approaches were utilized: primary BCG perfusion for RU with carcinoma in situ (CIS) (n=31), and percutaneous resection with (n=54) or without (n=33) adjuvant BCG perfusion for RU with papillary NMI tumors. Recurrence was defined as positive selective UUT cytology after obtaining negative cytology for RU with CIS, and positive biopsy after the 3-month nephroscopy for RU undergoing resection. Progression was defined as an increase in grade or stage of primary tumor at time of recurrence. For the purpose of analysis, RU were stratified by initial treatment modality, primary BCG perfusion versus percutaneous resection. RU undergoing percutaneous resection were stratified by adjuvant BCG therapy. Outcome measures were recurrence, progression, and renal preservation rate, time to recurrence and overall survival. Chi-square and independent t tests were used for comparison of all outcome measures between these strata. RESULTS: Mean and median follow up was 61.8±55.8 and 42 months, respectively. There was no statistical difference in tumor grade or stage between BCG-treated and non-treated RU (p>.05). Overall progression rate was 19.9%, diminishing to 6.5% for RU with CIS. Overall renal preservation rate was 84.7%, reaching 93.5% for RU with CIS. No statistically significant difference between the above mentioned strata was found in the outcome measures (p>.05). All results are detailed in the table. CONCLUSIONS: Our data suggests that organ-sparing treatment of NMI UUT TCC yields a relatively high (>75%) renal preservation rate. The use of adjuvant BCG therapy after resection appeared not to have an impact on recurrence, progression, renal preservation rate, time to recurrence, and overall survival. BCG perfusion seems to give the best results in patients with UUT CIS. Source of Funding: None
377 ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CARCINOMA IN PATIENTS WITH HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME) Scott G Hubosky*, Sarah Charles, Bruce Bowman, Demetrius H Bagley, Philadelphia, PA INTRODUCTION AND OBJECTIVE: Hereditary nonpolyposis colorectal cancer is a genetic disorder associated with extracolonic
136
THE JOURNAL OF UROLOGY®
malignancies including upper tract urothelial carcinoma of the ureter and renal pelvis. The disorder is characterized by mutations in DNA mismatch repair genes including MSH-2 and MLH-1. Patients tend to present at younger ages compared to sporadic cases of upper tract urothelial cancer and the incidence of bilateral renal involvement is unknown in this particular population. We retrospectively studied the clinical characteristics and outcomes of 10 patients with HNPCC to determine the efficacy of endourological management and surveillance. METHODS: Our experience with ureteroscopic management of upper tract urothelial carcinoma was retrospectively reviewed and 8 patients were identified having MSH-2 genetic mutations consistent with HNPCC; 2 patients are pending genetic workup but provide strong clinical suspicion for HNPCC based on personal and family history. Records were reviewed to determine age at presentation, bilaterality of disease, number of surveillances, months of follow-up and disease progression. RESULTS: No patients developed metastatic upper tract urothelial carcinoma; one died of metastatic colon cancer after a third recurrence. Mean age at presentation was 57 years (40 - 73), mean number of surveillances was 10.2 (2 - 30), mean months of followup 48 (3 - 152). 40% of patients had bilateral disease; 6 patients had ureteral involvement and 4 patients had renal pelvis involvement. All cases presented as grade 1-2 and no cases progressed to grade 3. One nephroureterectomy was performed after ureteral stricture development; final pathology showed CIS of the renal pelvis. CONCLUSIONS: This series is the first reported on HNPCC patients with upper tract urothelial involvement undergoing endoscopic surveillance and treatment. Endoscopic management is attractive in this patient population in which relatively younger patients may present with bilateral disease. Close endoscopic surveillance is paramount to avoid disease progression. Source of Funding: None
378 ODMIT C: A PROSPECTIVE RANDOMISED MULTICENTRE TRIAL OF A SINGLE POST-OPERATIVE DOSE OF INTRAVESICAL MITOMYCIN C TO PREVENT BLADDER CANCER FORMATION FOLLOWING NEPHROURETERECTOMY FOR UPPER TRACT TCC ( UTTCC) Tim S O’Brien*, Raj Singh, Eleanor Ray, Bola Coker, Ralph Beard, London, United Kingdom; BAUS Section of Oncology INTRODUCTION AND OBJECTIVE: Bladder tumours are reported in upto 40% of patients following surgery for an upper tract TCC. The evidence suggests that many of these bladder tumours may be implantation metastases. Reducing this risk of bladder tumour formation would be a valuable contribution in the management of these patients. Prophylactic intravesical chemotherapy has never been formally tested in this regard. METHODS: Patients with UTTCC and no previous history of bladder cancer were entered by 46 centres in the UK between July 2000 and December 2006. Patients were randomised to receive standard care or a single post operative dose of 40 mg intravesical Mitomycin-C on removal of the urethral catheter following nephroureterectomy. Follow up was by cystoscopy at 3/12, 6/12 and 12/12. The primary endpoint was the development of bladder tumour within the first year post-nephroureterectomy. The trial was supported by BAUS sub-section of Oncology. RESULTS: 284 patients were randomised. The number of cases per centre ranged from 1-21. The arms were well matched for age and tumour multifocality; however in the mitomycin treated arm there were more grade 3 tumours (51 versus 43). There were 31 exclusions ( 6 no tumour; 8 RCC; 3 other tumour not TCC; 11 protocol violations; 3 others ). There were no reported serious adverse effects from Mitomycin C. 5 patients were unable to retain the mitomycin for one hour. By intention to treat, bladder recurrence occurred in 21/122 (17%) of the mitomycin arm and 33/123 (26%) of the observation arm (P = 0.05). By treatment received, bladder recurrence occurred in 17/106 (16%) of the mitomycin arm and 31/119 (26%) of the observation arm (P = 0.03). Bladder tumour was identified in 1/18 (6%) patients who had Grade 1 UTTCC; 31/122 (25%) who had grade 2 UTTCC;
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
and 20/94 (21%) who had Grade 3 UTTCC. The number needed to treat to prevent one bladder tumour in the first year post surgery is 10. CONCLUSIONS: A single intravesical dose of mitomycin-C helps prevent bladder tumour formation following nephroureterectomy for TCC. It should be considered in all patients. Source of Funding: £4000 was received from Kyowa to defer administrative costs of the trial
379 DO CHANGES IN RENAL FUNCTION FOLLOWING NEPHROURETERECTOMY IMPACT THE USE OF PERIOPERATIVE CHEMOTHERAPY? Rebecca L. O’Malley*, Matthew Kaag, Padraic O’Malley, Guilherme Godoy, New York, NY; Mang L Chen, Marc C. Smaldone, Ronald L. Hrebinko, Jr, Pittsburgh, PA; Kinjal C Vora, Bernard H Bochner, Guido Dalbagni, Michael D Stifelman, Samir S. Taneja, William C. Huang, New York, NY INTRODUCTION AND OBJECTIVE: Upcoming 2009 NCCN (National Comprehensive Cancer Network) guidelines for the management of upper tract transitional cell carcinoma (UTTCC) suggest that cisplatin-based chemotherapy (CBCT) in combination with surgery should be considered in selected patients. Unfortunately there is no level I evidence demonstrating the appropriate timing or efficacy of perioperative chemotherapy in UTTCC. Delivery of CBCT requires adequate renal function which may be significantly impaired following nephroureterectomy (NU). As a result we speculate that a significant number of patients may become ineligible for CBCT following NU. METHODS: We combined 3 institutional databases and identified 324 patients having undergone NU from 1991 to 2008. Patients receiving preoperative chemotherapy were excluded. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) by the Modification by Diet in Renal Disease equation (eGFR = 186 x [Serum Cr] -1.154 x Age-0.203 x [1.21 if African-American] x [0.742 if Female]). The serum Cr level drawn prior to surgery and the level drawn nearest to 3 months postoperatively (range 2 weeks-12 months) but prior to initiation of postoperative chemotherapy were utilized. Based on current cisplatinbased regimens for transitional cell carcinoma of the bladder we used estimated eGFRs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2 as potential eligibility cutoffs for CBCT. RESULTS: The median age of our cohort was 71 (IQR 63, 77), 9 (3%) were African-American and 192 (59%) were male. Based on cutoffs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2, 44% and 78% of patients respectively were eligible for CBCT prior to NU. Following NU only 15% and 53% remained eligible for CBCT based on cutoffs of 60 ml/min/1.73m2 and 45 ml/min/1.73m2, respectively. The reduction in eligible patients demonstrated statistical significance by either cutoff (p<0.001 for both). Of the 112 patients with borderline GFR (45 - 60 ml/ min/1.73m2) prior to NU, only 50 (45%) remained eligible for modified CBCT regimens following NU. CONCLUSIONS: For UTTCC there is a significant need for appropriately designed clinical trials assessing the timing and use of perioperative chemotherapy. Given the current findings the design of these trials must take into account the impact of NU on the eligibility of these patients for CBCT. Source of Funding: None
380 DEVELOPMENT OF CHRONIC KIDNEY DISEASE AFTER NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA AND IMPLICATIONS FOR THE ADMINISTRATION OF CISPLATIN-BASED CHEMOTHERAPY Brian R Lane*, Armine K Smith, Benjamin T Larson, Michael C Gong, Inderbir S Gill, Steven C Campbell, Andrew J Stephenson, Cleveland, OH INTRODUCTION AND OBJECTIVE: Neoadjuvant cisplatinbased chemotherapy (GC/MVAC) improves the survival of patients with invasive bladder cancer and adjuvant GC/MVAC is justified largely by